Woman experiences foreign body sensation, irritation in right eye
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A 69-year-old woman presented to an outside provider with foreign body sensation and irritation in the right eye for 3 days.
She had a medical history of rheumatoid arthritis and systemic lupus erythematosus and was on monthly infliximab infusions, hydroxychloroquine and maintenance prednisone. She had an ocular history of three penetrating keratoplasty surgeries and was on topical prednisolone acetate 1%.
Source: William W. Binotti, MD, and Melina Morkin, MD
The patient denied any recent history of trauma. Review of symptoms was positive for recent joint inflammation/flares, which was treated with an oral steroid taper, and she was currently being maintained on a maintenance dose of prednisone 5 mg per day.
A paracentral corneal infiltrate without an ulcer was noted on exam. Corneal scraping for culture was performed, a bandage contact lens was placed, and the patient was started on moxifloxacin four times a day. On follow-up 5 days later, she presented with ocular pain, a 2-mm corneal ulcer and a 1-mm hypopyon and was subsequently referred to the New England Eye Center.
Examination
Visual acuity was hand motion in the right eye. IOP was soft to palpation in the right eye and 15 mm Hg in the left eye. The pupil was round, slow to react and without a relative afferent pupillary defect in the right eye. Extraocular movements were full. On biomicroscopy exam, there was significant conjunctival injection, diffuse corneal haze, corneal graft with central elevation with a temporal 2-mm ulcer (Figure 1, top) and staining with underlying infiltrate. The cornea was noted to have more than 50% thinning next to the area of ulceration (Figure 1, bottom). Additionally, the ocular exam was notable for peripheral corneal neovascularization and a 1-mm hypopyon. The left eye was unremarkable except for blepharitis, punctate epithelial erosion and a posterior chamber IOL.
What is your diagnosis?
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Corneal ulcer
An infectious corneal ulcer is at the top of the differential and should be managed as such until proven otherwise. Inflammatory corneal ulcers should also be in the differential diagnosis, especially with a history of autoimmune diseases. These include peripheral ulcerative keratitis, interstitial keratitis, Mooren ulcer, mucous membrane pemphigoid and marginal keratitis. One should also suspect chronic use or abuse of topical anesthetic and trauma with the eye drop bottle. Of note, there was no evidence of corneal perforation; however, given a history of keratoplasty and examination of focal corneal thinning, one should always carefully inspect for corneal perforation.
Management
Corneal cultures for bacteria, fungus, virus and Acanthamoeba were performed. Fortified vancomycin and fortified tobramycin every hour in the right eye were started, and the prednisolone acetate 1% and moxifloxacin were stopped. The patient was advised to sleep with a protective eye shield and educated on alarming ocular signs with daily follow-up. Her corneal cultures were positive for Candida albicans and Staphylococcus epidermidis. Thus, topical amphotericin B was added to the treatment. On the second day of follow-up, she presented with eye pain and a small corneal perforation at the temporal area, which was managed with tissue glue. Her vision was hand motion in the right eye at that visit. Three days later, her right eye pain slightly worsened and became constant. Her exam showed no signs of leakage or new perforation but enlarged hypopyon of 2 mm. A B-scan was performed and demonstrated concerns for vitreous debris (Figure 2) that was not present on prior visit. Therefore, the suspicion for keratitis-related endophthalmitis was raised. In the setting of constant pain, slightly worsened hypopyon and new vitreous debris in an immunosuppressed patient with previous PK, the decision was ultimately reached to perform a vitreous aspiration for cultures and intravitreal injection of vancomycin and voriconazole. She was then admitted to the ICU due to poor social support for the demanding hourly fortified drops and frequent follow-ups.
Her clinical course was notable for significant improvement of ocular pain on day 5 of hospitalization, with slow and gradual improvement of hypopyon, corneal ulcer and infiltrate. The results from the vitreous biopsy showed no growth on culture, and no cells were visualized on gram stain. Her eye continued to improve clinically, but she had a prolonged hospital stay due to monitoring a prolonged QTc interval. Eventually, she was discharged from the hospital after 29 days and followed in clinic. Her vision remained hand motion in the right eye after the corneal ulcer and infiltrate had resolved.
Discussion
Worldwide, fungal keratitis constitutes up to 50% of all microbial keratitis. In the United States, fungi account for 6% to 20% of corneal infections. The most common risk factors include trauma with soil or plant material, contact lens wear, ocular surface disease, chronic use or abuse of topical medications (corticosteroids, anesthetics and antibiotics), immunosuppression and previous ocular surgery. The clinical presentation can be insidious and often overlaps between symptoms and signs of bacterial infection, making early diagnosis challenging. Clinical findings alone are unable to differentiate between bacterial and fungal keratitis. Thus, corneal scraping for cultures is indicated in all suspected cases. The latter has a wide range of sensitivity reported in the literature (27% to 78%), attributed to susceptibility of the technique and experience, whereas RNA polymerase chain reaction provides rapid diagnosis with higher sensitivity and specificity (greater than 90%). Additional ancillary testing, such as in vivo confocal microscopy, can aid in diagnosis and monitoring of treatment response. Moreover, anterior segment OCT can accurately measure the corneal thinning and the viability of the graft-host junction of prior keratoplasty.
The most commonly isolated organisms in fungal keratitis are Fusarium (42.2%) and Aspergillus (32.8%). Candida species accounts for only 1.3% of isolated organisms, mainly in immunosuppressed individuals. Available treatments include natamycin, amphotericin B, voriconazole and ketoconazole, which should be tailored to the cultured organism and susceptibility. Fungal keratitis can be challenging to diagnose and manage. A study by Sharma and colleagues revealed an overall mean healing time of 45.8 ± 27.6 days on topical and systemic antifungals. Early diagnosis and treatment are key for successful outcomes. Intrastromal and intracameral injections of antifungals have been proposed by some authors when deep stromal layers of the cornea are involved. However, there is no consensus as to whether these significantly affect final outcomes. Cyanoacrylate glue can be utilized in cases of small corneal perforations or a descemetocele. Conversely, therapeutic PK is indicated for perforation or imminent perforation. In such cases, infection recurrence rates can range from 5% to 14% in the literature. Those at higher risk for recurrence are those cases with an associated hypopyon or limbal involvement. Mundra and colleagues reported a mean graft survival of 5.9 months in the setting of fungal keratitis.
In severe cases, microorganisms from the corneal ulcer can invade locally or enter the anterior chamber through an already perforated cornea, propagating the infection to the posterior segment of the eye with many cases of fungal keratitis-related endophthalmitis reported in the literature. In a study by Wan and colleagues, out of 392 patients with severe refractory fungal keratitis, 37 patients (9.4%) had endophthalmitis. They identified associated risk factors such as the use of topical steroids, previous suturing of a corneal laceration, corneal ulcer size of 10 mm or larger, hypopyon and aphakia. Seven of the 37 eyes (18.9%) were eviscerated in this study, highlighting the potential devastating outcomes. Nearly two-thirds of patients with fungal endophthalmitis lost useful vision. In contrast to bacterial endophthalmitis, in which the Endophthalmitis Vitrectomy Study confirmed the benefit of posterior vitrectomy in patients with light perception vision or worse, there are no current guidelines for fungal endophthalmitis. Hence, treatment should be tailored to each case.
- References:
- Donovan C, et al. Surv Ophthalmol. 2022;doi:10.1016/j.survophthal.2021.08.002.
- Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol. 1995;doi:10.1001/archopht.1995.01100120009001.
- Liu MY, et al. Eur J Ophthalmol. 2020;doi:10.1177/1120672119833896.
- Miller D, et al. Fungal keratitis, In: Mannis MJ, et al. Cornea Fundamentals, Diagnosis and Management. Elsevier. 5th ed. Elsevier; 2022:880-895.
- Mundra J, et al. Indian J Ophthalmol. 2019;doi:10.4103/ijo.IJO_1952_18.
- Sharma N, et al. Cornea. 2019;doi:10.1097/ICO.0000000000001781.
- Sharma N, et al. Ocul Surf. 2022;doi:10.1016/j.jtos.2021.12.001.
- Wan L, et al. Retina. 2019;doi:10.1097/IAE.0000000000002112.
- For more information:
- Edited by Jonathan T. Caranfa, MD, PharmD, and Angell Shi, MD, of New England Eye Center, Tufts University School of Medicine. They can be reached at jcaranfa@tuftsmedicalcenter.org and ashi@tuftsmedicalcenter.org.
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